The importance of individual components of immunologic function to the host's natural defense has been most clearly revealed when isolated deficiencies have led to clinical disease. Because such abnormalities can now be effectively detected and defined by new laboratory methods, diseases of immunodeficiency are being discovered with increasing frequency. Immunodeficiency disorders must be considered in two major categories: the primary immunodeficiency, often genetically determined, and secondary immunodeficiency states. The latter occur as complications of infections and infestations, gastrointestinal disorders, malnutrition, aging, lymphoid malignancies, other cancers and many other diseases. Immunodeficiency of varying severity is also encountered as a side effect of many treatment modalities, including radiation therapy and chemotherapy for cancer. From this perspective, the primary and secondary immunodeficiencies are not rare diseases. These problems have necessitated a search for novel therapeutic agents that have the property of immunopotentiation.
The discovery of the involvement of the immune system in the pathogenesis of an ever-increasing number of diseases has inevitably led to attempts to modify the course of these diseases, by manipulating the various elements of the immunological machinery. Stimulation of the immune system is invariably the choice for the mitigation of the immunodeficient state. This approach, for which there are several sets of potent agents (i.e. bacillus Calmette-Guerin, endotoxins) available today, holds particular promise in two major therapeutic areas in medicine—cancer and infectious diseases.
According to the concept of immunosurveillance, the immune system eliminates malignant cells when they appear. The role of T cells, and more recently of macrophages, natural killer cells against cancer has been reported. In addition, even if the antitumor immune response is not principally involved in the control of tumor growth, it is likely that adequate immunostimulation could elicit an effective immune response or render effective an otherwise ineffective response. All these considerations have justified the use of immunostimulation in the treatment of cancer, as an auxiliary method to surgery, radiotherapy or chemotherapy1.
Immunostimulants have also been extensively studied in infectious diseases in animal models. Infected subjects, who present a recognized immunodeficiency problem and often show infections with opportunistic microbes, should theoretically benefit from immunotherapy. It should be noted, however, that infections not obviously associated with immunodeficiency can also be treated with immunopotentiating agents, since enhancement of a immunological response may help to eliminate a particularly virulent agent which depresses normal physiological responses. Furthermore, particular attention should be given to the case of aging subjects, who often respond poorly to a number of vaccines (e.g. influenza).